Using Mechanistic Modeling Approaches to Support Bioequivalence Assessments for Oral Products

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Regulatory Science
• Pharmaceutical Development

Background:

• The 2022 workshop focused on best practices for utilizing modeling and simulation in generic product development.
• Mechanistic modeling, particularly PBPK, is increasingly important for demonstrating bioequivalence (BE).
• Current challenges include standardizing PBPK approaches for oral drug products.

Purpose of the Study:

• To summarize discussions on mechanistic modeling for BE assessments of oral drug products.
• To identify strategies for integrating PBPK modeling into regulatory submissions.
• To foster best practices for PBPK modeling in generic drug development.

Main Methods:

• Summary of proceedings from a joint FDA and CRCG workshop.
• Discussion of case studies and general strategies for PBPK absorption modeling.
• Exploration of regulatory pathways for PBPK modeling applications.

Main Results:

• General strategies and frameworks for PBPK modeling of oral products are emerging with successful case studies.
• The utility of PBPK modeling is growing, aiding in the development of generic oral drugs.
• Increased PBPK absorption modeling cases are being developed and shared.

Conclusions:

• PBPK modeling is a key tool for modernizing bioequivalence assessments in generic drug development.
• Establishing general strategies will accelerate the evolution and adoption of PBPK modeling.
• Early communication between industry and regulatory agencies (e.g., pre-ANDA meetings) is vital for successful PBPK implementation.